Failure to synthesize the T Cell CD3-? chain: Structure and function of a partial T cell receptor complex

Sussman, Jeffrey J.; Bonifacino, Juan S.; Lippincott‐Schwartz, Jennifer; Weissman, Allan M.; Saito, Takashi; Klausner, Richard D.; Ashwell, Jonathan D.

doi:10.1016/0092-8674(88)90533-8

Cited by 331 publications

(230 citation statements)

References 42 publications

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“…These excess chains that remain as free subunits or as partiaUy assembled complexes are largely transported to lysosomes and are rapidly degraded. Subsequent studies on a k-deficient T cell hybridoma variant, MA5.8, revealed that the ~ chain determines the normal post-Golgi fate of the CD3/Ti complex (Sussman et al, 1988a). The k-minus complexes formed in this cell line are transported normally from the ER to the Golgi.…”

Section: Discussionmentioning

confidence: 99%

“…Consistent with the biosynthetic studies in 2B4 cells are more recent observations made in variant T cells lacking expression of the ~ chain. In such cells, partial, five-member complexes were found to be routed to lysosomes where they were rapidly degraded (Sussman et al, 1988a).…”

mentioning

confidence: 99%

“…Several studies in both the human and murine systems have shown the importance of concomitant expression of both Ti-a and Ti-13 with the CD3 chains and ~ for cell surface expression of the TCR. In T cell mutants lacking Ti-a (Schmitt-Verhulst et al, 1987;Saito et al, 1987a), Ti-~ (Weiss and Stobo, 1984;Sussman et al, 1988b), or ~ (Sussman et al, 1988a, marked reduction in surface expression of the remaining TCR chains occurs. Transfecting the genes for Ti-ct or Ti-13 into mutant cells deficient in the synthesis of these chains can restore surface expression of functional TCRs in these cells (Ohashi et al, 1985;Saito et al, 1987b).…”

mentioning

confidence: 99%

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Selective degradation of T cell antigen receptor chains retained in a pre-Golgi compartment.

Chen

Bonifacino

Yuan

et al. 1988

The Journal of Cell Biology

139

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Abstract. We have examined the fate of newly synthesized T cell antigen receptor (TCR) subunits in a T cell hybridoma deficient in expression of the clonotypic 13 chain. Synthesis and assembly of the remaining chains proceed normally but surface expression of TCR chains is undetectable in these cells. A variety of biochemical and morphological techniques has been used to show that the TCR chains in these cells fail to be transported to any of the Golgi cisternae. Instead, they are retained in a pre-Golgi compartment which is either part of or closely related to the endoplasmic reticulum. The CD3-6 chain is degraded by a nonlysosomal process that is inhibited at temperatures at or below 27°C. By contrast, the remaining chains (CD3-e, CD3-'t, and ~) are very stable over 7 h. We propose possible mechanisms that may explain the differential fate of TCR chains retained in a pre-Golgi compartment.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Selective degradation of T cell antigen receptor chains retained in a pre-Golgi compartment.

Chen

Bonifacino

Yuan

et al. 1988

The Journal of Cell Biology

139

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“…Interference with the normal synthesis, degradation, transport, or processing of gene transcripts coding for the various TCR/CD3 chains would prohibit expression of the antigenreceptor complex (35,36). Mature (23)(24)(25)(26)(27)(28).…”

Section: Discussionmentioning

confidence: 99%

A specific defect in CD3 gamma-chain gene transcription results in loss of T-cell receptor/CD3 expression late after human immunodeficiency virus infection of a CD4+ T-cell line.

Willard-Gallo¹,

Keere²,

Kettmann³

1990

Proc. Natl. Acad. Sci. U.S.A.

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“…The endoplasmic reticulum is the natural site of Ab assembly, being the residence of molecular chaperones that assist in the correct folding of Ig molecules (34). Presumably, in CD3 ϩ cell lines the ␣CEA ϫ ␣CD3 dAb interacted with newly synthesized CD3 ⑀-chains in the endoplasmic reticulum, and the complex was degraded (35,36). Transfected Jurkat cells showed a normal pattern of expression of surface TCR/CD3 (data not shown).…”

Section: Design and Expression Of A Bispecific ␣Ceaϫ␣cd3 Two-chain Dabmentioning

confidence: 99%

Induction of Human T Lymphocyte Cytotoxicity and Inhibition of Tumor Growth by Tumor-Specific Diabody-Based Molecules Secreted from Gene-Modified Bystander Cells

Blanco

Holliger

Vile

et al. 2003

The Journal of Immunology

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Infiltrating T cells are found in many malignancies, but they appear to be mostly anergic and do not attack the tumor, presumably because of the absence of activation and/or costimulatory signals. We describe a strategy for cellular antitumor immunotherapy by the in situ production of soluble bifunctional Ab-based molecules that activate and retarget T cells to the tumor. We genetically modified cells to simultaneously secrete two bifunctional molecules, a bispecific diabody directed against the carcinoembryonic Ag (CEA) and the CD3ε chain of the TCR (αCEA × αCD3), and a fusion protein comprising the extracellular portion of B7-1 fused to a bivalent anti-CEA diabody (B7-αCEA). Together, αCEA × αCD3 and B7-αCEA proved potent at inducing the activation, proliferation, and survival of primary human T cells. When producer cells were cocultured with primary T cells and CEA+ cancer cells, αCEA × αCD3 and B7-αCEA acted in combination to activate and retarget T cell cytotoxicity and completely abrogate tumor growth in the coculture. Furthermore, the introduction of just a few such producer cells at the tumor site efficiently inhibited the growth of established human colon carcinoma xenografts. Despite a cumbersome generation process, the use of autologous gene-modified producer cells opens the way for a new diabody-based gene therapy strategy of cancer.

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Failure to synthesize the T Cell CD3-? chain: Structure and function of a partial T cell receptor complex

Cited by 331 publications

References 42 publications

Selective degradation of T cell antigen receptor chains retained in a pre-Golgi compartment.

Selective degradation of T cell antigen receptor chains retained in a pre-Golgi compartment.

A specific defect in CD3 gamma-chain gene transcription results in loss of T-cell receptor/CD3 expression late after human immunodeficiency virus infection of a CD4+ T-cell line.

Induction of Human T Lymphocyte Cytotoxicity and Inhibition of Tumor Growth by Tumor-Specific Diabody-Based Molecules Secreted from Gene-Modified Bystander Cells

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